Abstract 15407: Pentaerythrityl Tetranitrate Treatment Improves Left Ventricular Function and Reduces Mitochondrial Superoxide Anion-Production in Rats With Ischemic Heart Failure
Reduced nitric oxide (NO) bioavailability contributes to progression of heart failure. Organic nitrates can liberate NO, however long-term treatment is limited by development of tolerance and stimulation of reactive oxygen species (ROS) formation by most nitrates. We therefore sought to investigate the effects of long-term pentaerythrityl tetranitrate (PETN), an organic nitrate devoid of tolerance development, in rats with heart failure (CHF) after extensive myocardial infarction (MI). Starting 7 days after coronary artery ligation, rats were randomly selected for a 9 week treatment with PETN (80 mg/kg twice daily by gavage) or placebo (PLA). Rats with extensive MI size (PETN, 51±1%; PLA, 53±1%) developed elevated LV filling pressure (PETN, 24±4 mmHg; PLA, 26±3 mmHg), and similarly reduced LV systolic pressure. Long-term PETN therapy versus placebo reduced right atrial pressure (5.3±0.6, versus 11±2 mmHg, p<0.05) and substantially improved LV contractility (dP/dtmax, 7710±869 versus 5372±313 mmHg/s, p<0.01). PETN treatment also significantly increased LV ejection fraction (50±4 versus 38±2%, p<0.05), and cardiac index (280±20 versus 214±10 mL/min?kg, p<0.01), and prevented the rightward shift of the pressure-volume curve. Moreover, PETN therapy significantly diminished the increased superoxide anion production (measured by MitoSOX™Red-based HPLC-EC method) in the mitochondria from failing LV myocardium. Long-term treatment with PETN prevented LV functional deterioration and structural dilation and reduced mitochondrial superoxide anion production in CHF rats after MI. PETN therefore might be a promising therapeutic option in heart failure treatment.
- © 2010 by American Heart Association, Inc.